Losing a sister to breast cancer over a decade ago inspired Karen S. Aboody, M.D., to make the battle against cancer her life's work.

Dr. Aboody is at the forefront of research into using neural stem cells to assist in the delivery of chemotherapy to brain tumors, a critical step in attacking invasive tumors that cannot be successfully treated through surgery or other means.

A member of the City of Hope staff since 2003, Dr. Aboody received her medical degree at New York's Mount Sinai School of Medicine and received further training at Harvard Medical School.

Neural Stem Cell-Mediated Cancer Treatment

Overview: Neural stem cells (NSCs) have a natural ability to home to malignant tumors and invasive tumor cells, making them an ideal delivery vehicle for transporting therapeutic agents to tumor sites. Dr. Aboody and colleagues at COH were the first in the world to move this therapeutic strategy from “bench to bedside” for brain tumor patients, demonstrating safety of their NSCs.

My translational research laboratory focuses on neural stem cells (NSCs) and their therapeutic applications for primary and metastatic tumors. Our novel findings have demonstrated the inherent tumor-tropic property of NSCs, and their use as cellular delivery vehicles to effectively target and deliver therapeutic payloads to invasive tumor sites, including brain tumors and metastatic cancers. Their capacity for tracking infiltrating tumor cells and localizing to distant micro-tumor foci make NSCs a novel and attractive tumor selective delivery vehicle with tremendous clinical potential. In effect, the NSCs serve as a platform for tumor-localized therapy, which should also minimize toxicity to normal tissues. Our current research focuses on modifying human NSCs to deliver different therapeutic agents to tumor sites in animal models.

Clinical Trials: In 2013, we completed a first in-human FDA approved safety/feasibility NSC clinical trial at City of Hope in patients with recurrent high-grade gliomas (clinical PI: Dr. Jana Portnow, MD). The NSCs delivered an enzyme (cytosine deaminase; CD) that converts an inactive prodrug (5-flurocytosine; 5-FC) to an active chemotherapeutic agent (5-Flurouracil; 5-FU). The 5-FU produced by the NSCs diffuses into surrounding brain tumor tissue, selectively killing dividing tumor cells. By producing the chemo drug only at the tumor sites, systemic side effects are minimized. Results of this study demonstrated: 1) safety of administering therapeutic NSCs into the brain tumor resection cavity or biopsy site; 2) proof of concept for tumor-localized chemotherapy production – demonstrating that the CD-expressing NSCs were able to convert oral 5-FC to the active chemo drug 5-FU, locally in the brain; and 3) no significant immune response following one round of treatment. A phase I dose escalation, multi-treatment round study is currently accruing patients at COH.

NSCs are genetically modified to express cytosine deaminase (CD). When the inactive prodrug 5-FC is administered, it crosses the BBB and gets converted to the active chemotherapeutic 5-FU by the CD expressing NSCs locally at the brain tumor sites. In effect, allowing for tumor localized chemotherapy production, and reducing toxic side effects to normal tissues.

In 2010, we were granted an $18M CIRM Disease Team Award to move a 2nd generation enzyme/prodrug therapeutic toward clinical trials (Co-PIs: Jana Portnow, MD and Larry Couture, PhD). Collaborators include the Synold lab for pharmacology, the Barish lab for 3D tumor reconstruction, the Forman lab (C Brown) for xenogen imaging and tumor modeling, and the Moats lab at Children’s Hospital Los Angeles for MRI imaging. We also work closely with the Center for Biomedicine & Genetics and the Office of IND Development and Regulatory Affairs. An IND has been submitted and we expect to initiate a phase I study for this NSC-mediated brain tumor therapy in 2015. We are also funded $4.7M by an NIH-U01 (in collaboration with CHLA and St. Jude) to move this same product to clinical trial for pediatric patients with metastatic neuroblastoma by 2017.

Aboody K, Capela A, Niazi N, Stern JH, Temple S: Translating stem cell studies to the clinic for CNS repair: Current state of the art and the need for a rosetta stone. Neuron 2011 May 26;70(4):597 613.